Three Cochrane reviews commissioned by the World Health Organization evaluate GLP-1 receptor agonists like tirzepatide, semaglutide, and liraglutide for weight loss in people with obesity. The drugs show substantial weight reduction compared to placebo, but researchers note limitations in long-term data and industry funding influences. Side effects such as nausea are common, raising questions about broader access and safety.
Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for type 2 diabetes in the mid-2000s, have shown benefits in managing blood sugar, reducing heart and kidney risks, supporting weight loss, and lowering early death rates in diabetic patients with comorbidities.
Recent testing has extended their use to obesity treatment. These medications mimic a hormone that slows digestion and promotes fullness. In the United Kingdom, they are approved for weight management alongside diet and exercise for those with obesity or overweight with related conditions.
The reviews analyzed randomized controlled trials for three key drugs:
- Tirzepatide (Mounjaro and Zepbound), given weekly, resulted in about 16% average weight loss after 12 to 18 months, based on eight trials with 6,361 participants. Benefits may persist up to 3.5 years, though long-term safety data is limited.
- Semaglutide (Ozempic, Wegovy, and Rybelsus), also weekly injections, achieved roughly 11% weight loss after 24 to 68 weeks, from 18 trials involving 27,949 participants. Effects can last up to two years, with more participants losing at least 5% of body weight, but gastrointestinal side effects were more frequent.
- Liraglutide (Victoza and Saxenda), a daily injection, yielded 4-5% average weight loss, drawn from 24 trials with 9,937 participants. Evidence beyond two years is scarce.
No significant differences appeared in major cardiovascular events, quality of life, or mortality compared to placebo. However, side effects like nausea led some to discontinue treatment.
"These drugs have the potential to bring about substantial weight loss, particularly in the first year," said Juan Franco, co-lead researcher from Heinrich Heine University Düsseldorf, Germany.
A major concern is that many studies were funded and conducted by drug manufacturers, potentially creating conflicts of interest. Researchers call for more independent research.
Access remains a barrier due to high costs for semaglutide and tirzepatide, though liraglutide is more affordable post-patent expiration; semaglutide's patent ends in 2026. Trials were mostly in middle- and high-income countries, underrepresenting areas like Africa and Southeast Asia.
"We need more data on the long-term effects and other outcomes related to cardiovascular health, particularly in lower-risk individuals," said Eva Madrid, co-lead researcher from the Universidad de Valparaíso, Chile.
These findings will shape upcoming WHO guidelines on GLP-1 drugs for obesity.
